Tuberculosis, especially among the elderly, still remains a health problem in the United States. Adverse reactions to anti-TB drugs are frequent in the elderly, attributable in part to a lack of information on drug-drug interactions for TB drugs and to inappropriate dose regimens that are derived from pharmacokinetic data obtained in young adults. The proposed studies seek to obtain pharmacokinetic parameters of three anti-TB drugs, isoniazid, (INH), ethambutol (EMB), and rifampicin (RIF), given singly or in combinations, in TB patients of different age groups. The data obtained from these studies will be important in establishing guidelines for optimum dosing and scheduling of anti-TB drugs given in combinations, especially in the elderly. Twenty studies in four patients receiving one or more of the anti-TB drugs RIF, INH, and EMB have been carried out. Preliminary studies indicate several clinically important interactions of these drugs. Co-administration of the three drugs resulted in high plasma levels (2-3 fold) of EMB as compared to cases where EMB was administered with only INH. Plasma levels of INH were increased by co-administration with EMB and decreased with RIF; the effect appeared to be correlated with the rate of INH acetylation, which was suppressed by EMB and stimulated by RIF (the latter in young and not in old patients). The interaction of the anti-TB drugs at the plasma protein binding sites was insignificant. Our recent finding of irreversible (covalent) binding between INH and plasma proteins may be of significance regarding the known side effects of INH.